Assembly Of Hydrogels Research Articles

Polysaccharide and poly(methacrylic acid) based biodegradable elastomeric biocompatible semi-IPN hydrogel for controlled drug delivery

Nanoparticles embedded semi-interpenetrating (semi-IPNs) polymeric hydrogels with enhanced mechanical toughness and biocompatibility could have splendid biomedical acceptance. Here we propose poly(methacrylic acid) grafted polysaccharide based semi-IPNs filled with nanoclay via in situ Michael type reaction associated with covalent crosslinking with N,N-methylenebisacrylamide (MBA). The effect of nanoclay in the semi-IPN hydrogel has been investigated which showed significant improvement of mechanical robustness. Meanwhile, the hydrogels showed reversible ductility up to 70% in response to cyclic loading-unloading cycle which is an obvious phenomenon of rubber-like elasticity. The synthesized semi-IPN hydrogel show biodegradability and non-cytotoxic nature against human cells. The live-dead assay showed that the prepared hydrogel is a viable platform for cell growth without causing severe cell death. The in vitro drug release study in psychological pH (pH = 7.4) reveals that the controlled drug release phenomena can be tuned by simulating the environment pH. Such features in a single hydrogel assembly can propose this as high performance; biodegradable and non-cytotoxic 3D scaffold based promising biomaterial for tissue engineering.

Self-assembled three-dimensional reduced graphene oxide-based hydrogel for highly efficient and facile removal of pharmaceutical compounds from aqueous solution

Herein, self-assembled three-dimensional reduced graphene oxide (RGO)-based hydrogels were synthesized and characterized in detail. A thorough investigation on the uptake of three widely used pharmaceutical drugs, viz. Naproxen (NPX), Ibuprofen (IBP) and Diclofenac (DFC) was carried out from aqueous solutions. To ensure the sustainability of developed hydrogel assembly, practically important parameters such as desorption, recyclability and applicability to real samples were also evaluated. Using the developed 3D hydrogels as adsorptive platforms, excellent decontamination for the above mentioned persistent pharmaceutical drugs was achieved in acidic pH with a removal efficiency in the range of 70–80%. These hydrogels showed fast adsorption kinetics and experimental findings were fitted to different kinetic models, such as pseudo-first order, pseudo-second order, intra-particle and the Elovich models in an attempt to better understand the adsorption kinetics. Furthermore, equilibrium adsorption data was fitted to the Langmuir and Freundlich models, where relatively higher R2 values obtained in case of former one suggested that monolayer adsorption played an important part in drug uptake. Thermodynamic aspects were also studied and negative ΔG0 values obtained indicated the spontaneous nature of adsorption process. The study was also extended to check practical utility of as-prepared hydrogels by spiking real aqueous samples with drug solution, where high % recoveries obtained for NPX, IBP and DFC were of particular importance with regard to prospective application in wastewater treatment systems. We advocate RGO-based hydrogels as environmentally benign, readily recoverable/recyclable material with excellent adsorption capacity for application in wastewater purification.

The effect of metal ions on the viscoelastic properties of thermosensitive sol-to-gel reversible metallo-supramolecular hydrogels

Fine-tuning of thermo-induced assembly and rheological behaviour of hydrogels based on a copolymer having two distinct hydrophilic blocks via metal ions.

G4-quartet hydrogels from 5'-hydrazino-guanosine for the non-covalent and covalent remediation of contaminants from water.

The creation of supramolecular hydrogels from relatively simple building blocks demonstrates the power of molecular self-assembly to make functional materials. G4-quartet hydrogels are appealing for a number of applications, including the environmental remediation of pollutants in water. We find that the guanosine analog, 5'-deoxy-5'-hydrazinoguanosine (HG 2) self-assembles into a self-standing hydrogel in the presence of stoichiometric amounts (0.25 equiv.) of KCl. The higher water solubility of HG 2 (14.5 mM), compared to that of the parent compound G 1 (2.1 mM), likely contributes to its enhanced gelation. The structural basis for this HG 2·KCl hydrogel, confirmed by PXRD, IR and CD, is the G4·K+ quartet, which forms extended 1D ion-channel assemblies that entangle to give a stable and long-lived hydrogel. We also find that adding KCl to a saturated solution of HG 2 triggers the generation of colloidal G4·K+ assemblies in situ that selectively and efficiently binds the anionic dye naphthol blue black (NBB) over a cationic dye. In addition to this non-covalent electrostatic binding of anions, the nucleophilic 5'-hydrazino group in the HG 2·KCl hydrogel HG 2 enables the efficient absorption of propionaldehyde from both the gas phase and from water solution via the formation of covalent hydrazone linkages with the gel matrix.

Conformation-Directed Formation of Self-Healing Diblock Copolypeptide Hydrogels via Polyion Complexation.

Synthetic diblock copolypeptides were designed to incorporate oppositely charged ionic segments that form β-sheet-structured hydrogel assemblies via polyion complexation when mixed in aqueous media. The observed chain conformation directed assembly was found to be required for efficient hydrogel formation and provided distinct and useful properties to these hydrogels, including self-healing after deformation, microporous architecture, and stability against dilution in aqueous media. While many promising self-assembled materials have been prepared using disordered or liquid coacervate polyion complex (PIC) assemblies, the use of ordered chain conformations in PIC assemblies to direct formation of new supramolecular morphologies is unprecedented. The promising attributes and unique features of the β-sheet-structured PIC hydrogels described here highlight the potential of harnessing conformational order derived from PIC assembly to create new supramolecular materials.

Environmental‐Friendly Assembly of Functional Graphene Hydrogels with Excellent Antibacterial Properties

AbstractBacterial contamination, harmful to human beings health and well‐being, has been a serious issue in china, even in the modern world. Graphene‐based materials have been found to have good antimicrobial properties. However, the research on three‐dimensional graphene related material with excellent antimicrobial activity is quite limited, which hinders its usage in protection of environment and sustainable development, such as in water treatment. In this work, we successfully design a facile, green and efficient strategy to fabricate three‐dimensional graphene hydrogel monoliths with excellent antibacterial properties by zinc ions coordination. The presence of zinc ions can maintain the structural integrity and the resulting sample exhibits excellent antimicrobial activities toward E. coli (99.5 ±3.6 %) and S. aureus (96.4 ±4.6 %) with increased glutathione oxidation capacity. The mechanism is also intensively investigated. The whole preparation process is carried out without using any toxic reducing agent, which may offer an alternative strategy for the fabrication of graphene related materials with excellent antibacterial properties.

Temperature-responsive nanogel multilayers of poly(N-vinylcaprolactam) for topical drug delivery

We report nanothin temperature-responsive hydrogel films of poly(N-vinylcaprolactam) nanoparticles (νPVCL) with remarkably high loading capacity for topical drug delivery. Highly swollen (νPVCL)n multilayer hydrogels, where n denotes the number of nanoparticle layers, are produced by layer-by-layer hydrogen-bonded assembly of core-shell PVCL-co-acrylic acid nanoparticles with linear PVPON followed by cross-linking of the acrylic acid shell with either ethylene diamine (EDA) or adipic acid dihydrazide (AAD). We demonstrate that a (νPVCL)5 film undergoes dramatic and reversible swelling up to 9 times its dry thickness at pH = 7.5, indicating 89v/v % of water inside the network. These hydrogels exhibit highly reversible ∼3-fold thickness changes with temperature variations from 25 to 50°C at pH = 5, the average pH of human skin. We also show that a (νPVCL)30 hydrogel loaded with ∼120µgcm−2 sodium diclofenac, a non-steroidal anti-inflammatory drug used for osteoarthritis pain management, provides sustained permeation of this drug through an artificial skin membrane for up to 24h at 32°C (the average human skin surface temperature). The cumulative amount of diclofenac transported at 32°C from the (νPVCL)30 hydrogel after 24h is 12 times higher than that from the (νPVCL)30 hydrogel at 22°C. Finally, we demonstrate that the (νPVCL) hydrogels can be used for multiple drug delivery by inclusion of Nile red, fluorescein and DAPI dyes within the νPVCL nanoparticles prior to hydrogel assembly. Using confocal microscopy we observed the presence of separate dye-loaded νPVCL compartments within the hydrogel matrix with all three dyes confined to the nanogel particles without intermixing between the dyes. Our study provides opportunity for development of temperature-responsive multilayer hydrogel coatings made via the assembly of core-shell nanogel particles which can be used for skin-sensitive materials for topical drug delivery.

Three-Dimensional Calcium Alginate Hydrogel Assembly via TiOPc-Based Light-Induced Controllable Electrodeposition

Artificial reconstruction of three-dimensional (3D) hydrogel microstructures would greatly contribute to tissue assembly in vitro, and has been widely applied in tissue engineering and drug screening. Recent technological advances in the assembly of functional hydrogel microstructures such as microfluidic, 3D bioprinting, and micromold-based 3D hydrogel fabrication methods have enabled the formation of 3D tissue constructs. However, they still lack flexibility and high efficiency, which restrict their application in 3D tissue constructs. Alternatively, we report a feasible method for the fabrication and reconstruction of customized 3D hydrogel blocks. Arbitrary hydrogel microstructures were fabricated in situ via flexible and rapid light-addressable electrodeposition. To demonstrate the versatility of this method, the higher-order assembly of 3D hydrogel blocks was investigated using a constant direct current (DC) voltage (6 V) applied between two electrodes for 20–120 s. In addition to the plane-based two-dimensional (2D) assembly, hierarchical structures—including multi-layer 3D hydrogel structures and vessel-shaped structures—could be assembled using the proposed method. Overall, we developed a platform that enables researchers to construct complex 3D hydrogel microstructures efficiently and simply, which has the potential to facilitate research on drug screening and 3D tissue constructs.

Three-dimensional polypyrrole-derived carbon nanotube framework for dye adsorption and electrochemical supercapacitor

Three-dimensional carbon nanotube frameworks have been prepared via pyrolysis of polypyrrole nanotube aerogels that are synthesized by the simultaneous self-degraded template synthesis and hydrogel assembly followed by freeze-drying. The microstructure and composition of the materials are investigated by thermal gravimetric analysis, Raman spectrum, X-ray photoelectron spectroscopy, transmission electron microscopy, and specific surface analyzer. The results confirm the formation of three-dimensional carbon nanotube frameworks with low density, high mechanical properties, and high specific surface area. Compared with PPy aerogel precursor, the as-prepared three-dimensional carbon nanotube frameworks exhibit outstanding adsorption capacity towards organic dyes. Moreover, electrochemical tests show that the products possess high specific capacitance, good rate capability and excellent cycling performance with no capacitance loss over 1000 cycles. These characteristics collectively indicate the potential of three-dimensional polypyrrole-derived carbon nanotube framework as a promising macroscopic device for the applications in environmental and energy storages.

Mechanistic Insights into the Directed Assembly of Hydrogel Blocks Mediated by Polyelectrolytes or Microgels.

In this study, we report the directed assembly of hydrogel blocks mediated by electrostatic interactions. We compared two different assembly mechanisms, one mediated by microgel particles and another mediated by direct interaction between oppositely charged blocks. The system consisted of hydrogel blocks made of an interpenetrated network of (hydroxyethyl)methacrylate-poly(ethylene glycol)dimethacrylate (HEMA-PEGDMA) and either positively charged polyethylenimine (PEI) or negatively charged hyaluronic acid (HA). Positively charged hydrogel blocks were pretreated with negatively charged microgel particles (MG) made of N-isopropylacrylamide-methacrylic acid. Both systems (PEI/HA and PEI/MG) demonstrated spontaneous directed assembly, meaning that positive blocks were systematically found in contact with oppositely charged blocks. Directed assembly in water of PEI/HA blocks resulted in large and open aggregates, while PEI/MG blocks exhibited more compact aggregates. Effects of salt and pH were also assessed for both systems. Inhibition of blocks aggregation was found to appear above a critical salt concentration (CSalt*) which was significantly higher for the PEI/HA system (80 mM) compared to the PEI/MG system (5-20 mM). The observed difference was interpreted in terms of the nanostructure of the contact area between blocks. Blocks aggregation was also found to be controlled by the content of negatively charged groups in the microgels as well as the concentration of MG in the suspension (CMG) used to treat the hydrogel block surfaces. Our results shine light on the subtle differences underlying the adhesion mechanisms between hydrogel blocks and suggest new routes toward the design of innovative complex soft materials.

Synthesis of polyacid nanogels: pH-responsive sub-100 nm particles for functionalisation and fluorescent hydrogel assembly.

Nanogels are crosslinked polymer particles with a swollen size between 1 and 100 nm. They are of major interest for advanced surface coatings, drug delivery, diagnostics and biomaterials. Synthesising polyacid nanogels that show triggered swelling using a scalable approach is a key objective of polymer colloid chemistry. Inspired by the ability of polar surfaces to enhance nanoparticle stabilisation, we report the first examples of pH-responsive polyacid nanogels containing high -COOH contents prepared by a simple, scalable, aqueous method. To demonstrate their functionalisation potential, glycidyl methacrylate was reacted with the -COOH chemical handles and the nanogels were converted to macro-crosslinkers. The concentrated (functionalised) nanogel dispersions retained their pH-responsiveness, were shear-thinning and formed physical gels at pH 7.4. The nanogels were covalently interlinked via free-radical coupling at 37 °C to form transparent, ductile, hydrogels. Mixing of the functionalised nanogels with polymer dots enabled covalent assembly of fluorescent hydrogels.

Reversible Modulation of DNA-Based Hydrogel Shapes by Internal Stress Interactions.

We present the assembly of asymmetric two-layer hybrid DNA-based hydrogels revealing stimuli-triggered reversibly modulated shape transitions. Asymmetric, linear hydrogels that include layer-selective switchable stimuli-responsive elements that control the hydrogel stiffness are designed. Trigger-induced stress in one of the layers results in the bending of the linear hybrid structure, thereby minimizing the elastic free energy of the systems. The removal of the stress by a counter-trigger restores the original linear bilayer hydrogel. The stiffness of the DNA hydrogel layers is controlled by thermal, pH (i-motif), K+ ion/crown ether (G-quadruplexes), chemical (pH-doped polyaniline), or biocatalytic (glucose oxidase/urease) triggers. A theoretical model relating the experimental bending radius of curvatures of the hydrogels with the Young's moduli and geometrical parameters of the hydrogels is provided. Promising applications of shape-regulated stimuli-responsive asymmetric hydrogels include their use as valves, actuators, sensors, and drug delivery devices.

Protein-Nanoparticle Hydrogels That Self-assemble in Response to Peptide-Based Molecular Recognition.

Recently, supramolecular hydrogels assembled through nonspecific interactions between polymers and nanoparticles (termed PNP systems) were reported to have rapid shear-thinning and self-healing properties amenable for cell-delivery applications in regenerative medicine. Here, we introduce protein engineering concepts into the design of a new family of PNP hydrogels to enable direct control over the polymer-nanoparticle interactions using peptide-based molecular recognition motifs. Specifically, we have designed a bifunctional peptide that induces supramolecular hydrogel assembly between hydroxy apatite nanoparticles and an engineered, recombinant protein. We demonstrate that this supramolecular assembly critically requires molecular recognition, as no assembly is observed in the presence of control peptides with a scrambled amino acid sequence. Titration of the bifunctional peptide enables direct control over the number of physical cross-links within the system and hence the resulting hydrogel mechanical properties. As with previous PNP systems, these materials are rapidly shear-thinning and self-healing. As proof-of-concept, we demonstrate that these materials are suitable for therapeutic cell delivery applications in a preclinical murine calvarial defect model.

Counterion‐Directed Assembly: Counterion‐Directed, Structurally Tunable Assembly of Hydrogels, Membranes, and Sacs at Aqueous Liquid–Liquid Interfaces (Adv. Mater. Interfaces 5/2016)

Counterion‐Directed Assembly: Counterion‐Directed, Structurally Tunable Assembly of Hydrogels, Membranes, and Sacs at Aqueous Liquid–Liquid Interfaces (Adv. Mater. Interfaces 5/2016)

Hydrogel Assembly with Hierarchical Alignment by Balancing Electrostatic Forces

Hydrogel Assembly with Hierarchical Alignment by Balancing Electrostatic Forces

Counterion‐Directed, Structurally Tunable Assembly of Hydrogels, Membranes, and Sacs at Aqueous Liquid–Liquid Interfaces

Counterions play a crucial role in directing the self‐assembly of components in biological systems. In this paper, the self‐assembly of aromatic dipeptides and polysaccharide chitosan is reported at an aqueous liquid–liquid interface. It is shown that subtle modulations in the counterions and pH values allow changes in the self‐assembling pathway localized at the aqueous liquid–liquid interface and thus fabricate materials with distinct structural features and functions, from hydrogels to membranes and hollow sacs. The hydrogel shows strong birefringence and the directional freeze of the gel leads to the formation of macroscopically layered domains with sizes up to centimeters. Moreover, the membranes and sacs exhibit high mechanical strengths, tunable permeabilities, and pH‐responsiveness and have good performance for controlled release. Compared with other self‐assembling peptides, aromatic dipeptides are much smaller and easier to synthesize (low cost). The self‐assembly of these dipeptides with functional polysaccharide chitosan has potential applications in many areas, including large‐scale manufacture of microcapsules for controlled drug release and enzyme immobilization.

Engineering the intestinal basement membrane microenvironment using PEG-based hydrogels

Event Abstract Back to Event Engineering the intestinal basement membrane microenvironment using PEG-based hydrogels Victor Hernandez-Gordillo1, Gi Hun Choi1, Mollie Smoak2, Rebecca Carrier3 and Linda Griffith1 1 Massachusetts Institute of Technology, Biological Engineering, United States 2 Louisiana State University and Agricultural Center, Department of Biological and Agricultural Engineering, United States 3 Northeastern University, Department of Chemical Engineering, United States Introduction: Intestinal organoids or “mini-guts” are multilobulated structures composed of budding crypts, epithelial cells and well-defined lumens. Mini-guts have gained interest as a tool to study intestinal biology and as a platform for drug screening because they resemble aspects of the intestinal complexity found in vivo[1]. Mini-guts are cultured embedded in ill-defined Matrigel-based hydrogels. Lot-to-lot variability and the presence of residual growth factors in Matrigel can negatively impact the biological outcomes. Thus, the development of a well-defined matrix that can recapitulate aspects of the basement membrane for intestinal organoid culture is of vital importance. Poly(ethylene glycol, PEG)-based hydrogels are good candidates as synthetic matrices. They can be tailored to different applications by varying the stiffness, degradability and cell adhesion properties. Here we report our efforts to develop PEG-based hydrogels functionalized with a fibronectin-derived peptide (SYNK-RGDS) or a collagen-derived peptide (GFOGER) for intestinal organoid culture. Materials and Methods: Hydrogels were prepared by first reacting a 40 KDa, 8-arm PEG-vinyl sulfone with cell adhesive peptides containing single free thiols groups. Then cross-linked using matrix metalloproteinase sensitive peptides harboring two free thiols groups. We incorporated two fibronectin-derived peptides (RGDS and SYNK-RGDS) and one derived from collagen (GFOGER). Single intestinal stem cells were embedded in these hydrogels either directly during hydrogel assembly or indirectly using a two-step encapsulation. The two-step encapsulation allowed us to modulate the stiffness and cell adhesion properties of the bottom and top hydrogel. Results and Discussion: Preliminary results suggest that direct encapsulation of single cells obtained from mouse organoids in these PEG-based hydrogels results in formation of organoids similar to those that form in Matrigel (Fig. 1b). The PEG-GFOGER hydrogel showed higher number of organoids when compared to PEG-Synk-RGDS hydrogel. A two steps encapsulation procedure with varying stiffness and cell adhesion properties resulted in a completely different morphology. Mouse cells developed multicellular growth structures that resemble the villi of the intestine (Fig. 1c). Further analysis will be needed to confirm the identity of these structures. Figure 1. a) Overall strategy to created PEG-Based hydrogels. b-c) Representative confocal image of mouse intestinal stem cells directly embedded b) or two-steps embedding strategy c) after 7 days of culture in PEG-GFOGER hydrogel systems. Actin is depicted in green and nuclei in blue. Conclusions: We were able to identify hydrogel culture conditions that allow single mouse cells to develop into three-dimensional structures that resemble mouse organoids in direct cell encapsulation or multicellular growth that resembles the villi when using two stem cell encapsulation. DARPA; NIH; Boston Children Hospital

Self-assembly and controllable synthesis of graphene hydrogel adsorbents with enhanced removal of ciprofloxacin from aqueous solutions

A convenient and efficient approach was applied for the assembly of graphene hydrogel (GH) adsorbents for the enhanced removal of ciprofloxacin (CIP) from an aqueous solution.

A bioinspired reversible snapping hydrogel assembly

Typical hydrogels undergo slow and continuous shape change. Inspired by the Venus Flytrap, the current work presents a hydrogel assembly that can reversibly undergo a non-continuous rapid snapping shape change due to a bi-stable structure of the assembly. In particular, the reversible snapping change goes beyond the Venus Flytrap and is not known in the literature.

ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function

SummaryThe mechanisms by which mutations in FUS and other RNA binding proteins cause ALS and FTD remain controversial. We propose a model in which low-complexity (LC) domains of FUS drive its physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids. These assemblies are necessary and sufficient for neurotoxicity in a C. elegans model of FUS-dependent neurodegeneration. They trap other ribonucleoprotein (RNP) granule components and disrupt RNP granule function. One consequence is impairment of new protein synthesis by cytoplasmic RNP granules in axon terminals, where RNP granules regulate local RNA metabolism and translation. Nuclear FUS granules may be similarly affected. Inhibiting formation of these fibrillar hydrogel assemblies mitigates neurotoxicity and suggests a potential therapeutic strategy that may also be applicable to ALS/FTD associated with mutations in other RNA binding proteins.